Development of a Novel Bio-Adhesive Mesh System for Abdominal Hernia Repair Project Summary/Abstract This project proposes the development of a novel mesh-adhesive system for abdominal hernia repair utilizing surface modification of polymer surgical mesh to allow for improved tissue fixation with a poloxamine hydrogel adhesive. More than 1 million Americans undergo hernia repair with surgical mesh each year, most commonly with polypropylene (PP) mesh, with associated annual healthcare costs in excess of $3 billion. During abdominal hernia repair, a majority of surgical meshes are fixed to abdominal tissue by mechanical devices (e.g. sutures, staples, tacks) or tissue adhesives (e.g. fibrin sealant, cyanoacrylate-based glue). Mechanical devices are difficult to employ laparoscopically and can cause substantial post-operative pain. As such, fixation with tissue adhesives has been attempted, particularly for laparoscopic surgeries. However, cyanoacrylate-based glues leave brittle residues and have elevated toxicity when used on intra-abdominal tissues. Likewise, fibrin sealants do not provide immediate fixation between the mesh and tissues, and so in larger (>3 cm) hernia defects, additional mechanical devices such as sutures are needed to prevent edge curling and mesh slippage. To address these shortcomings, we propose to evaluate the combined application of two patented Clemson University technologies: a bifunctional poloxamine hydrogel adhesive and a surface modification technique to improve the adhesive strength between the hydrogel adhesive and polymer surgical meshes. The proposed hydrogel adhesive is non-toxic to cells in culture over a 12-day degradation period. It is biocompatible and safe as a tissue adhesive for treatment of small soft tissue wounds, eliciting a controlled inflammatory response in vivo without provoking unwanted tissue adhesions when used on intra-abdominal tissues. Although it exhibits an adhesive strength exceeding 70 kPa between tissues via mechanical interdigitation and covalent bond formation with tissue amines, the adhesive strength when used on unmodified PP mesh is inadequate. Therefore, a patented surface modification technique will be employed to provide a poly-glycidyl methacrylate (PGMA) layer grafted to human serum albumin (HSA) to form a three-dimensional plastic albumin. In our initial tests of adhesive strengths for meshes attached to collagen sheets with the hydrogel adhesive, the modified PP mesh using PGMA/HSA grafting resulted in significantly improved adhesive strength compared to unmodified meshes. Further development of our mesh-adhesive system will enable grafting of autologous proteins derived from the patient?s own blood onto PP surgical mesh at the time of surgery, thereby avoiding the potential for immunological reactions to foreign proteins on the mesh surface. This approach ultimately provides a complete solution for suture-less large hernia defect repair with immediate mesh fixation using our hydrogel adhesive, which will limit post-operative complications and hernia recurrence as part of a simplified laparoscopic procedure.